The preventive effect of deep sea water on the development of cancerous skin cells through the induction of autophagic cell death in UVB-damaged HaCaT keratinocyte.

Ultraviolet light (UV) is a major inducer of skin cancer. Therefore, recovery and removal of UV-damaged skin cells are important in the prevention of skin carcinogenesis. Here, we investigated the effect of deep sea water (DSW) in HaCaT keratinocyte exposed by UVB (λ = 290∼320 nm). The result showed that UVB-induced cell death was reinforced by DSW treatment in a hardness-dependent manner. Furthermore, the increase of cell death by DSW was associated with the down-regulation of survivin and RAD51 expressions induced by UVB. Moreover, we confirmed the inhibition of H2 A.X phosphorylation, a marker for double-stranded DNA damage, and the enhancement of LC3-II and SQSTM1/p62 expressions by DSW administration in UVB-radiated HaCaT keratinocyte. The results imply that the enhancement of UVB-induced cell death by DSW is associated with autophagy. Therefore, we further explored the regulation of autophagy-regulating proteins and apoptosis-related factors expression. Phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6, and S6 kinase by UVB radiation were regressed via DSW treatment, underlying the increase of AMP-activated protein kinase (AMPK) phosphorylation. Furthermore, UVB-enhanced nuclear factor κB (NF-κB) and c-Jun N-terminal kinase (JNK) phosphorylations were increased with DSW treatment. Contrastingly, DSW lessened the Ser15 phosphorylation of p53 and cleavage of poly (ADP-ribose) polymerase induced by UVB radiation. Consequently, the results demonstrate that DSW enhances UVB-damaged skin cell clearance through the activation of autophagic cell death underlying the regulation of AMP-activated protein kinase (AMPK)/mTOR signaling as well as NF-κB and JNK phosphorylations. In conclusion, this investigation suggests that DSW is a potent candidate for the prevention of UV-induced skin cancer development.